The proposed investigations will examine the structure of neuronal and astrocytic membranes in the mammalian central nervous system with freeze-fracture and thin-section electron microscopic techniques. The sequential acquisition of specialized membrane structure at the synaptic junctions of several classes of synapse will be examined and compared, and then the ways in which these orderly events may be deranged will be studied in strains of mutant mice characterized by aberrations of synaptogenesis. The formation of synaptic junctions and spinous evaginations will be compared with the process by which postsynaptic specializations are removed after destruction of the afferent. The investigation of neuronal membrane structure will include examination of axonal and dendritic growth cones and a search for changes in the neuronal plasmalemma which may accompany denervation. In the study of astrocytes, an effort will be made to determine whether the dramatic changes in astrocyte membrane structure that follow circulatory arrest reflect changes in pO2, pCO2, or pH, and to seek correlations between membrane changes and astrocytic swelling. Several variations of freeze-fracture methodology are to be used, especially rapid freezing and deep etching, so that sequelae of morphological techniques can be dissociated from native structure.